This invention generally pertains to piperazinyl- and piperidinyl-cyclohexenes and analogous cyclohexanes having anti-ischemic, antipsychotic and other bio-affecting properties and to their preparation and use. In some preferred embodiments, the invention is concerned with 1,4-disubstituted piperazine or piperidine derivatives wherein the 4-substituent is benzyl or substituted benzyl, and the 1-substituent is a 1-aryl-cyclohexen-4-yl or a 1-aryl-cyclohexan-4-yl moiety. These compounds and others structurally related thereto possess a unique profile that makes them useful in the treatment of ischemia-induced illnesses and psychosis.
Caprathe et al. disclosed a series of piperazinyl-cyclohexene compounds characterized by structural formula A in U.S. Pat. No. 4,975,445. Formula A is: ##STR3## wherein R' is an aryl or heterocyclic ring, a is 0-2 and b is 0-4.
As can be seen, these earlier compounds are chemically distinguishable from the instant compounds on the basis of their chemical structures because they are aryl- or heteroaryl-piperazines, whereas the instant compounds are benzyl- or heteroarylmethyl-piperazines (when, in Formula I below, Y.dbd.N) or -piperidines (when, in Formula I below, Y.dbd.CH). Additionally, these earlier compounds are biologically distinguishable from the instant compounds, since the earlier compounds possess dopaminergic properties, which are associated with undesirable side effects including Parkinsonism and extrapyramidal side effects such as catalepsy. Contrastingly, the instant compounds are devoid of dopaminergic properties and the movement disorders often associated therewith.
U.S. Pat. No. 4,954,502 to Smith et al discloses compounds of the following formula: ##STR4## wherein A may be a C.sub.5-7 cycloalkyl ring. The compounds are taught to be antidepressants. There is no suggestion in the patent that these compounds are useful in the treatment of stroke or other ischemia-based conditions.
Caprathe et al disclosed a series of piperazinyl-cyclohexanol compounds characterized by structural formula B in U.S. Pat. No. 4,957,921. Formula B is: ##STR5## wherein n is 0 to 4 and Ar and Ar' are aryl or heterocyclic rings. Likewise, these compounds are structurally and biologically distinguishable from the instant compounds. Chemically, the reference compounds are aryl-piperazines, while the instant compounds are benzyl- or heteroarylmethyl-piperazines. Biologically, their dopaminergic properties distinguish them from applicants' compounds, which do not have dopaminergic activity. Accordingly, the movement disorders associated with dopaminergic agents are avoided when the instant compounds are administered.